A relationship between pulmonary emphysema, proteolysis of alveolar tissue, and alpha-proteinase inhibitor (alpha-1-antitrypsin) deficiency has been clearly established. The objective of this proposal are to demonstrate that normal alpha-1-proteinase inhibitor can be inactivated by oxidation of its active site methionine residue. Two mechanisms which, under certain conditions would be expected to be found coincidentally with it in vivo, will be investigated. The first involves the action of the myeloperoxidase-hydrogen peroxide-chloride ion system and the second involves the production and utilization of singlet oxygen as a inactivating agent. The methods to be used include enzyme kinetics, amino acid analysis, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and laser irradiation for production of singlet oxygen.